Condyloma acuminata, commonly referred to as genital warts, are known to be benign, fibro-epithelial tumors associated with various papilloma viruses. Condyloma acuminata is a sexually-transmitted disease, the occurrence of which is increasing rapidly. Genital warts are frequently found on or near the vulva, in the vagina, and about the rectum or penis. The manifestation of genital warts begins as an itching sensation whereupon a small papule develops. Depending upon the extent of the lesion, continued itching and a discharge may occur.
A number of prior art treatments are known, including the use of cryotherapy and the surgical excision of the warts. Traditional treatment modalities also include the use of podophyllin which is applied topically to the lesions. Podophyllin treatment is typically repeated at intervals of seven to fourteen days and may cause irritation of the affected area.
It is known that interferons exert a broad spectrum of biological activity such as anti-viral, anti-proliferative and immunomodulatory activities. Following the characterization of interferon by Isaacs and Lindeman, interferon has been the subject of intense research to determine its molecular structure and genetic basis as well as to develop processes for its synthesis and protocols for clinical applications. The exact mechanisms by which its anti-tumor, anti-viral and immune system activities occur are not fully understood. A number of references are available which detail the history and scope of interferon research such as DeMaeyer et al., "Interferons" appearing as Chapter 5 in Comparative Virology, Vol. 15, pp. 205-284, Plenum Press, N.Y., N.Y. (1979); Cantrell, "Why Is Interferon Not In Clinical Use Today" appearing in Interferon 1979, I. Gresser, ed., Vol. 1, pp. 1-28, Academic Press, London (1979); Stewart, "The Interferon System" Springer-Verlag, N.Y., N.Y. (1979); Dunnick, et al., "Clinical Trials with Exogenous Interferon," J. Infect. Diseases, 139, No. 1, pp. 109-123 (1979); and Proc. Rov. Soc. London (Ser. B), Vol. 147, pp. 256 et seq. (1957) and U.S. Pat. No. 3,699,222.
The nomenclature which has been adopted to classify interferons is generally standardized. To qualify as an interferon, a factor must be a protein which exerts non-specific, anti-viral activity at least in homologous cells through cellular metabolic processes involving synthesis of both RNA and protein. Interferon is abbreviated "IFN," and each interferon is identified according to the animal of origin. Thus, human interferon is designated "Hu IFN." Interferons are classified into types on the basis of antigenic specificities. Type designations for the most common interferons are alpha, beta and gamma which correspond to previous designations of leukocyte, fibroblast, and Type II (immune) interferons, respectively. Alpha and beta interferons are typically acid-stable with gamma interferons being acid labile. Interferons may be produced through genetic engineering and are generally referred to as "recombinant interferons." Recombinant interferons are designated in accordance with the foregoing nomenclature, for example, "Hu rIFN-.alpha." for human recombinant alpha interferon. For the purposes of the present invention, all references to alpha interferon will be to natural or non-recombinant human alpha interferon unless otherwise specified.
Human alpha interferon is known to be effective in the treatment of several viral infections, including chronic hepatitis B virus infections and herpes zoster infections ("Effect of Human Leukocyte Interferon on Hepatitis B Virus Infection in Patients with Chronic Active Hepatitis," N. Engl. J. Med., Vol. 295; "Human Leukocyte Interferon for the Treatment of Herpes Zoster in Patients with Cancer," N. Engl. J. Med., Vol. 298). More recently, human alpha interferon has been found to suppress the in vitro replication of AIDS virus ("Human Alpha- and Beta-Interferon but not Gamma Suppress the In Vitro Replication of LAV-HTLV-III and ARV-II," J. Interferon Res 6:143; "Direct and Cell-Mediated Effects of Interferon Alpha and Gamma on Cells Chronically Infected with HTLV-III," J. Interferon Res 6:543). Also, numerous techniques have been developed to purify interferon, for example the method described in U.S. Pat. No. 3,144,390 to Burke.
In addition, others have treated condyloma acuminata with recombinant human alpha-interferon by the subcutaneous and intramuscular injection of interferon. Both recombinant human alpha-interferon and human beta-interferon have been used in this manner. (See, G. Gross, et al., "Alpha-Interferon in Condylomata Acuminata and Juvenile Diabetes Mellitus," Dtsch-Med.-Wochenschr, 1986, Sep. 5, III(36), pp. 1351-5; A. Schonfeld, et al., "Intramuscular Human Interferon Beta Injections in Treatment of Condylomata Acuminata," Lancet, 1984, May 12, I(8385), pp. 1038-42). Treatment of condylomata acuminata with interferon typically involves injection directly into the warts. Associated side effects may include fever, chills, myalgia, headache, fatigue and leukopenia.
There are also known topical uses of interferon, for example, as a prophylactic which is effective against the transmission of rhinovirus infections between infected subjects and uninfected subjects. As described in "Prophylactic Efficacy of Intranasal Alpha-Interferon Against Rhinovirus Infections in the Family Setting," N. Engl. J. Med., Vol. 314, No. 2, the preparation and use of alpha-interferon along with a pharmaceutically acceptable excipient in the form of an intranasal spray is described. The alpha-interferon spray was administered as a metered aerosol. Topical application of alpha-interferon has also been used for the treatment of dendritic herpes keratitis.
Also, in U.S. Pat. No. 4,017,600, one of the inventors of the present invention describes a method for reactivating interferon using a combination of an agent for disrupting non-covalent bonds, an agent for reducing disulfide bridges, and an anionic or cationic surface-active agent. In U.S. Pat. No. 3,981,991, one of the inventors of the present invention describes a method for stabilizing interferon by treatment in the manner described in U.S. Pat. No. 4,017,600, and the use of sodium dodecyl sulfate is specifically disclosed.
The present invention provides a composition and a method for using this composition in the treatment of condyloma acuminata.